Researchers at Mass General Brigham and the University of Cyprus published a mechanistic model suggesting antibody-drug conjugate (ADC) delivery can improve by normalizing the tumor microenvironment while avoiding over-tightening tumor blood vessels. In bladder cancer, new work in Advanced Science found that the secreted tumor protein LRG1 binds ANXA2 in neutrophils, collapsing their mitochondrial function and triggering NET release—mechanisms the authors link to vessel growth and undermined chemo-immunotherapy. In pancreatic cancer, integrating single-cell and spatial transcriptomics uncovered an invasive-frontier fibroblast state that predicted poor survival and identified five repurposed drug candidates, pointing to microenvironment targets at the tumor edge. Together, these studies emphasize how tumor physiology and stromal/immune cell state determine therapeutic penetration, vascular support, and resistance to combination strategies.